Cancer is one of the deadliest illnesses in the United States. It accounts for nearly 600,000 deaths annually, and costs billions of dollars for those who suffer from the disease. This disease is in fact a diverse group of disorders, which can originate in almost any tissue of the body. In addition, cancers may be generated by multiple mechanisms including pathogenic infections, mutations, and environmental insults (see, e.g., Pratt et al., Hum. Pathol. 36:861-70, 2005). Current cancer treatments include, among others, surgery, chemotherapeutics, radiation therapy, immunotherapy, and photodynamic therapy. However, none of these treatments is completely effective, and each has its own associated side effects.
Hypoxia is a characteristic feature of many tumors, particularly locally advanced and recurrent solid cancers resulting from an imbalance between oxygen supply and consumption (see Vaupel et al., Oncologist 9 Suppl. 5:4-9, 2004). Cancer tumor hypoxia can reduce the effectiveness of radiotherapy, some oxygen-dependent cytotoxic agents, and photodynamic therapy. The presence of hypoxia has been demonstrated in a wide variety of human cancers, including colorectal, cervix, breast, lung, brain, pancreas, head and neck, and prostate. Many of these tumors contained regions of severe hypoxia (<5 mmHg oxygen). Clinically, the duration of disease and progression free survival correlates inversely with the degree of tumor hypoxia. For example, in patients with squamous carcinoma of the head and neck, the one-year disease-free survival was 78% for patients with median tumor pO2>10 mm Hg but only 22% for median pO2<10 mm (Brizel, et al., Int. J. Radiat. Oncol. Biol. Phys. 38:285-9, 1997). Hypoxic cells exhibit increased resistance to standard radiation and chemotherapy treatment programs, as these cells are relatively isolated from the blood supply and because radiation and chemotherapy preferentially kill rapidly dividing cell populations.
Pharmaceutical compounds which sensitize hypoxic cells to radiation therapy have shown promising results. However, there remain drawbacks to the safety and efficacy in the current methods.